Infectious Disease Faculty at Virginia Tech

Are you an Infectious Disease researcher at Virginia Tech? Would you like to have your research
program listed here? If so, contact Steve Melville (melville@vt.edu)
or Steve Boyle (smboyle@vt.edu) and they will add your name
and program description.

Program Summary: Mosquito-borne viruses are a global problem, with hundreds
of millions of infections
per year and more than a billion people at risk. The 1999 introduction of West Nile virus into North
America has reminded our culture of how frightening mosquito-borne diseases can be. In 2003, there
were 9,858 reported cases of West Nile, including 262 deaths. This contrasts with an estimated 50-100
million cases of dengue fever (DF), and as many as 500,000 cases of dengue hemorrhagic fever (DHF) per
year worldwide, resulting in 5,000-10,000 deaths. Currently, viruses such as West Nile virus, LaCrosse
virus, and eastern equine encephalitis virus circulate in the state of Virginia, threatening the
health and safety of its citizens. Mosquito species which are able of transmitting dengue viruses or
yellow fever virus are present in Virginia and in other parts of the U.S. Thus, there is the continual
risk of a reintroduction of these deadly viruses into the U.S.. My research program is comprised of
both basic and applied aspects. The basic research component focuses on both the viruses and the
mosquitoes. I seek to understand, at the molecular and genetic level, how these viruses infect,
replicate, and are transmitted by mosquitoes to humans. I also seek to understand the mosquito
immune response to these viruses, as unlike people, mosquitoes do not become ill when infected
with these deadly viruses. Only by understanding genetic changes in the mosquito, genetic
changes in the virus, as well as the effects of different environmental situations can we
truly hope to anticipate and prevent mosquito-borne viral outbreaks. The applied component
of my research focuses on using this information to design and implement new methods of
controlling or preventing mosquito-borne viral disease outbreaks. This includes using genetics
to block the mosquito’s ability to transmit viruses, and the development of new diagnostic tools
to identify mosquitoes which are more likely to participate in an outbreak.

Program Summary: Chronic inflammation is found at the core of the most devastating and costly
diseases afflicting people in the Commonwealth of Virginia, the U.S. and the world. Common
inflammatory features in obesity, diabetes, cardiovascular disease, hypertension and cancer
include the abnormal recruitment and activation of immune cells. For example, obese and diabetic
individuals have higher amounts of immune cells in fat than leaner subjects, whereas patients
with cardiovascular disease accumulate immune cells in their blood vessels. Low-grade chronic
inflammation significantly contributes to increased severity, more rapid disease progression,
and higher mortality rates. We have found that inflammatory processes in general, and
obesity-related inflammation in particular, can be attenuated nutritionally through
anti-inflammatory receptors found in the nucleus of cells. Interestingly, immune cells
are highly responsive to regulation through a nuclear receptor named peroxisome
proliferator-activated receptor ☐ (PPAR ☐). The long-term goal of my laboratory
is to identify novel, naturally occurring, orally active compounds that bind to this receptor
and elicit anti-inflammatory actions. I received funding from the Institute for Biomedical
and Public Health Sciences to further characterize the mechanisms by which one of the newly
identified botanical compounds, abscisic acid, ameliorates insulin resistance and obesity-related
inflammation. This funding has recently been leveraged with support from the National Institutes
of Health. Our findings in this area could be used as a proof-of-concept for supporting the
development of a botanical center at Virginia Tech aimed at the high-scale identification of
new botanicals with anti-inflammatory properties.

Program Summary: Many of the newly emerging diseases in humans, such as West Nile Virus,
Hantavirus and Lyme disease, are transmitted between animals and humans. In addition, many human
parasitic diseases use insect vectors or require intermediate hosts to survive. Understanding how
pathogens and parasites persist in nature and what ecological and environmental factors contribute to
disease emergence can assist with control efforts. The current focus of my research is on
understanding how biodiversity influences parasites and pathogens in natural systems.
Within this realm, I am examining two very different systems. The first system is a
host-parasite system involving amphibian and snail hosts and a trematode parasite. I am
experimentally examining how changes in the species composition of ponds can influence
infection in tadpoles, as well as exploring how features of the landscape influence
transmission of the parasite. The second system involves the normal bacterial community
that lives on the skin of amphibians. I am examining whether beneficial bacteria can actually
prevent infection of the skin with pathogens and whether environmental stressors can alter the
outcome of these species interactions. Ecological interactions between species and ongoing
environmental changes likely play key roles in the emergence of many diseases in both
wildlife and human populations. My research will provide insight into these processes
in natural systems.

Program Summary: My research area is toxicology and neuroscience, specifically in the area of
insecticides, since most act as nerve poisons. New and safer chemicals are urgently needed for
use in human disease control and agriculture. My research program includes studies on both
mammals and insects to design chemicals with good selectivity and which are focused on the
interactions of small organic molecules with protein receptors found on cell membranes.
These organic molecules can be drugs, peptides, neurotransmitters, or insecticides. Most
of my research is focused on the mechanisms of how these compounds are toxic to the nervous
system, along with investigation into the mechanisms of insecticide resistance. My research
approach is multidisciplinary and includes studies of whole animal toxicity, effects on the
nervous system, and actions on proteins at the biochemical level.

Program Summary: The immune system of animals and humans is a complex collection of cells that
allow the clearance of disease-producing microorganisms (pathogens) that have crossed the physical
barrier presented by the skin or mucous membranes. The immune system produces antibodies and other
cells that interact with the pathogens and causes them to be destroyed. When an animal is
injected with a vaccine (derived from the pathogen), it causes the immune system to produce
antibodies and cells that prevent the pathogen from causing disease. Our laboratory is working
to improve a vaccine (Brucella abortus RB51), created at VA Tech and approved by the United
States Department of Agriculture in 1996, to prevent the disease called brucellosis that occurs
in animals and humans. The vaccine improvement is aimed at other animal diseases by using the
original vaccine as a platform to stimulate the immune system to protect against not only brucellosis
but other diseases as well (e.g., anthrax). The impact of such a potent vaccine will reduce the cost
of producing healthy livestock and health care by preventing the spread of diseases from animals to humans.

Program Summary: La Crosse (LAC) virus is the leading cause of pediatric encephalitis in the
United States. Within the past decade, there has been a rapid emergence of the virus and its primary
mosquito vector in several southeastern states, including Virginia. This has corresponded to an
increase in numbers of human cases of LAC encephalitis in the U.S. and it has become necessary to
determine the extent of LAC virus activity in Virginia. This effort, however, is complicated by the
possible involvement of two non-native species of mosquitoes that have recently become established
in areas where the LAC virus is currently found. It has also been complicated by our inability,
because of time, effort, and costs, to directly assess mosquito populations over large areas.
As such, two hypotheses are being tested to address these problems. We hypothesize that
non-native mosquito vectors are contributing to the increased incidence of LAC virus and that
the presence of LAC virus antibody in canine blood can be used as a practical indicator of LAC
virus transmission rates to vertebrates, making it possible to use dogs as sentinel animals for
LAC virus activity and transmission risk to humans. We are testing this hypothesis in area-wide
studies in three regions in southwest Virginia using a combination of field surveys, and analytical,
molecular, and geospatial techniques. One of the regions (far southwestern Virginia) has reported
human cases of LAC encephalitis and LAC-positive mosquitoes, the second region has LAC-positive
mosquitoes but no human cases (New River Valley), and the third region has had neither human
cases nor LAC-positive mosquitoes (Shenandoah Valley).

Program Summary: Medicine in the 20th century was transformed by the contribution of organic
chemists who prepared dozens of life-saving pharmaceuticals. Even in the present genomic era,
new drugs will undoubtedly be responsible for huge improvements in human health. Our research
has resulted in the development of new drug candidates for clinical depression and Alzheimer's
memory loss, several of which have been granted U.S. patents. Currently, our main focus includes
prevention of the brain damage associated with Alzheimer's disease and the development of new
agents to limit the spread of malaria by the Anopheles mosquito.

Program Summary: The three processes required to sustain life on earth include respiration,
photosynthesis, and nitrogen fixation. All three of these involve oxidation and reduction
reactions. For example, during respiration (breathing) food sources are oxidized to form
carbon dioxide in a process that provides energy; during photosynthesis, plants use energy
from the sun to reduce carbon dioxide to form sugars (food). These oxidation and reduction
reactions occur at iron atoms that are found in complexes called iron-sulfur clusters. The
biological formation of iron-sulfur clusters is different for different organisms. For this
reason, and because formation of iron-sulfur clusters is required for an organism to survive,
disruption of this process in pathogenic organisms provides an ideal target for the development
of therapeutic agents. Furthermore, because photosynthesis and formation of nitrogenous
fertilizers can be limited by the availability of iron-sulfur clusters, any improvement in
iron-sulfur cluster formation by using genetic manipulation provides an avenue for increased
food production and development of disease resistant crops.

Program Summary: The NDSSL is pursuing an advanced research and development program for
interaction-based modeling, simulation, and associated analysis, experimental design, and decision support tools for
understanding large biological, information, social, and technological systems. Extremely detailed, multi-scale computer
simulations allow formal and experimental investigation of these systems. The need for such simulations is derived from
questions posed by scientists, policy makers, and planners involved with very large complex systems. The simulation
applications are underwritten by a theoretical program in discrete mathematics and theoretical computer science
that is sustained by more than a decade of experience with the interplay of research and application.

I am the PI for a research group in the NIH Modeling Infectious Disease Agent Study (MIDAS) network. Our project
models the spread of disease transmitted from person to person in urban areas, allowing for the assessment of prevention,
intervention, and response strategies by simulating the daily movements of synthetic individuals within an urban region.
Our models allow the user to specify the effects in detail of a pathogen on a specific person, and to assign different
effects to various people based on demographic characteristics. Through MIDAS, we have influenced national policy on
preparing for an influenza pandemic; through related work for DoD we are supporting the development of mitigation
strategies for military populations in a pandemic. In conjunction with population mobility models it can represent
behavioral reactions to an outbreak, including official interventions. As part of an NSF Human Social Dynamics grant,
NDSSL is using this model to study the co-evolution of social networks and disease transmission networks.

In addition, I am co-PI for a CDC Center of Excellence in Public Health Informatics led by Matt Samore at the
University of Utah. This project seeks to understand how public health decision makers can use epidemiological
models. Other projects at NDSSL relevant to infectious disease include creating spatial models of vector-borne
disease epidemiology and applying them to malaria in sub-Saharan Africa, and modeling the human immune system
in detail to study the dynamics of HIV recombination within an individual.

Program Summary: New antibiotics are needed for treating emerging pathogens (e.g., Mycobacterium),
antibiotic-resistant pathogens (e.g., Enterococcus, Staphylococcus aureus, and Methicillin-resistant
S.aureus, MRSA), and fungal pathogens (e.g., Candida spp.). In the U.S., MRSA infections in hospitalized
patients are estimated to increase theaverage hospitalization by 10 days and cost over $900M.
New affordable antimicrobials are also needed to help persons in the epidemic-prone Third World.
Further, new antibacterial and antifungal agents are needed owing to the loss in potency and
efficacy of current drugs. Our preliminary data indicate that several members of a novel class
of drugs caused an inhibition of growth at microgram concentrations against such pathogens as
S.aureus, MRSA, and C. albicans. These new antibiotics could potentially prevent and treat
topical infections, such as vaginitis (C. albicans), and prevent nasal colonization and transmission
of S.aureus and MRSA. Moreover, as data accumulate concerning the efficacies of these antibiotics,
our investigations may be extended to include designing antibiotics for treating more serious
systemic infections. Finally, discovering the mechanism of antimicrobial action of these novel
antibiotics will lead to the identification of new drug targets in pathogenic bacteria,
mycobacteria, and fungi.

Program Summary: Viral Mothers: Modernity, Risk, and Maternal Embodiment
The medical community has known since the late 1980s that HIV is passed through breast milk from
infected mothers to their babies. In the United States and other highly industrialized countries, HIV-positive
mothers receive medical advice not to breastfeed their babies. Because formula (or replacement) feeding
is considered normal in the U.S. and other similar nations, this public health protocol receives little attention.

In the global south, the AIDS epidemic threatens to disrupt breastfeeding’s traditional contribution to infant
health and survival, particularly in Sub-Saharan Africa where the seroprevalence among women of
childbearing age is high. Attention to the dangers of breastfeeding in the context of maternal HIV infection
has changed international public health guidelines concerning infant feeding, creating dissention in public
health efforts and confusing mothers who have long been taught the benefits of breast milk.
Most public debates about infant feeding, while attending to issues of health and well being, are also
fueled by social anxieties about mothers’ bodies and maternal roles in the modern era. Understanding how
cultural perceptions of mothers influence public health debates is crucial to making sure that the advice,
support, and treatment offered to HIV-positive mothers is appropriate and will contribute to overall health
and well being.

My analysis involves historical, cultural, and discourse-based interpretive methods, primarily
addressing figurations of mothers in public health debates, medical advice genres, and the mass media.
This methodology is similar to what I used in writing Mother’s Milk: Breastfeeding Controversies in American
Culture (Routledge 2003).

My preliminary findings in Viral Mothers suggest that the transmission of HIV through
breastfeeding evokes other contemporary concerns about bodies, germs, and the environment that affect all
of us, especially as we struggle with the significance of health, risk, and embodiment in the modern period.
Our fears about mothers who are infectious, or whose bodies contain toxic chemicals that can be transferred
to infants, are related to more generalized fears of contamination and contagion that seem to characterize our
era.

This is not a book that will show us how to separate real concerns from imagined ones. Rather, it
is a series of arguments that reveal how very real concerns are nevertheless imagined and experienced
through ideological constructions of maternity. Identifying these does not dissolve them, but demonstrates
everyone’s subjection to meaning systems that are connected to powerful institutions and cultural values.
I include biomedicine among these powerful institutions, whose values seemingly permeate most daily
behaviors in modern societies.

Program Summary: Pathogens are colonizing novel hosts with increasing frequency due to
global agricultural traffic and habitat alteration. Managing and mitigating these emerging
disease threats to humans and wildlife requires a detailed understanding of why populations
vary in susceptibility to diseases over space and time. My research program investigates
the ecological and evolutionary mechanisms that underlie pathogen susceptibility, from single
host individuals to multi-host communities. I currently study disease dynamics in the context
of two broad frameworks: 1) genetic and species-level diversity, and 2) environmental and
social stressors. I approach disease ecology from a multi-disciplinary perspective in order
to understand how stress, genetics, social behavior, community composition, and environmental
context interact dynamically to influence host disease susceptibility and pathogen transmission.
Ultimately, these studies will improve our understanding of the processes that underlie disease
emergence and spread in wild animal, domestic animal, and human populations.

Project Summary:Francisella tularensis is a Category A bacterial pathogen and the
etiologic of tularemia. Currently there is no approved vaccine for tularemia, and no
approved rapid, non-culture diagnostic test. Due to the threat of bioterrorism, improved
vaccines, diagnostic tests, and therapeutics are a high priority for F. tularensis and other
select agents. F. tularensis is reported to be encapsulated, which may be an important component
for virulence and a target for diagnostic test, but a capsule has never been isolated or
characterized from this bacterium. Our laboratory has isolated a novel glycolipid from
F. tularensis that is antigenic, and is upregulated under stress conditions. We are currently
conjugating this glycolipid to a protein to evaluate it as a subunit vaccine against tularemia
in mice. Furthermore, we have identified the putative capsule DNA locus and have made a mutant
that may be unable to export this glycolipid. Antibodies to this glycolipid are being raised for
use in diagnostic tests.

Histophilus somni is responsible for a wide variety of systemic diseases in cattle,
including meningitis, myocarditis, pneumonia, and septicemia. H. somni possesses a wide variety
of virulence factors, some of which our laboratory has characterized over the past 20 years.
Unlike most obligate mucosal pathogens and members of the Pasteurellaceae, H. somni produces an
exopolysaccharide and an excellent biofilm. We have recently determined that H. somni forms
this biofilm in vivo, in heart tissue and in the lungs. Our current work is focused on biofilm
formation in the natural bovine host, and the use of this system as a model for biofilm infections in humans.

Program Summary: Natural products have made a major contribution to drug discovery and
especially to cancer chemotherapy, with Taxol being the best-selling anticancer drug in history.
Research in our group is centered on the chemistry of biologically active natural products related
to cancer, with major areas being the chemistry and mechanism of action of the anti-cancer agent
Taxol, the discovery of new anticancer agents from plants, and biodiversity conservation and drug
discovery in tropical rain forests. Taxol works by binding to microtubules, and we are studying
this binding in collaboration with colleagues at State University of New York Binghamton, Emory
University, and Washington University. The aim of our work is to help in the design and synthesis
of potent and readily accessible Taxol analogs. We are also collaborating with scientists from
CytImmune Inc. in designing a nanoparticle-based drug delivery system and with a colleague at the
National Institutes of Health in the design of a new method for the treatment of prostate cancer.
In the natural products area, we are involved in a search for novel anti-cancer agents from Nature
in a major collaborative project that combines drug discovery from the rain forests and oceans of
Madagascar with biodiversity conservation and economic development for the Malagasy people. We are
also starting a new approach to the discovery of novel antimalarial drugs in collaboration with a
colleague at Georgetown University.

Program Summary: Malaria is responsible for the death of 1-2 million people annually. Most of
malaria’s victims are children under the age of five living in tropical areas of the world. The
emergence, over the past couple of decades, of parasites that are resistant to available drugs
has limited our treatment options. There is, therefore, an urgent need for the development of
new anti-malarial drugs. The malaria parasite, a single-cell organism, causes disease as it
reproduces within human red blood cells. As it grows, the parasite consumes its host cell from
the inside, devouring most of the red blood cell’s oxygen-carrying protein, hemoglobin. My
research aims to understand how the malaria parasite is able to pull off this massive catabolic
feat. We focus our attention on enzymes called peptidases, which chop hemoglobin into small pieces,
and ultimately, into its amino acid building blocks. By understanding how these peptidases work,
we hope to discover chinks in the parasite’s armor that could be exploited for the development of
peptidase inhibitors that have anti-malarial activity.

Program Summary: The emergence of infectious diseases is driven by social, cultural,
economic, political, and environmental processes. For example, urbanization, civil conflict, and
climate variability and change have all been linked to the spread of infectious diseases and/or
the range of disease vectors. These processes act at different scales and across scales to either
contribute to or prevent disease emergence. At the global scale, travelers can carry disease
agents around the world, while vectors can also be transferred through similar means. Climate
variability and change impact the range of vectors, with areas expanding or contracting based on
temperature and precipitation patterns at regional scales. Lastly, at fine scales, individual
behaviors and local environmental characteristics can result in the creation of vector habitat
in a community and around a home. Geospatial technologies, such as remote sensing and geographic
information systems (GIS), provide an effective way to evaluate the relationship between disease
emergence and the underlying human or environmental factors that play a role in that emergence.
Human and physical variables can be combined within a GIS to illuminate the ways in which processes
act, and interact, across spatial scales to result in disease emergence.

Program Summary: Many pathogenic bacteria encounter different environments during their
infectious cycle and their ability to adapt to these changes is mediated by global regulatory networks.
In particular, recent research has shown that bacterial virulence is often regulated by networks involved
in the process of “quorum-sensing” – the regulation of gene expression as a function of cell density.
My research focuses on the integration of computational analysis and collaboration with experiments to
discover novel components and achieve a more fundamental understanding of quorum-sensing networks in
bacteria. In the process, we have computationally discovered and experimentally verified novel genes
called small RNAs which play a critical role in the quorum-sensing pathway and in regulating virulence.
Considerable research suggests that many virulent bacteria can be rendered nonvirulent by the
inhibition of their quorum-sensing pathways. Therefore, research into quorum sensing may provide
a novel means of treating many common and damaging bacterial infections without the use of antibiotics.
Furthermore, biotechnological approaches designed to exploit beneficial quorum-sensing processes
may prove useful in improving industrial-scale production of natural or engineered bacterial products.
Thus, the study of quorum-sensing is important from a basic science perspective as well as for its
applications to medicine and biotechnology.

Program Summary: Tryptophan is an essential amino acid, serving as a building block in protein
synthesis. Tryptophan from food is oxidized to kynurenine and then to 3-hydroxykynurenine (3-HK) in
mammals. 3-HK is easily oxidized under physiological conditions, leading to the production of reactive
oxygen species. Reactive oxygen species are implicated in inflammation and disease. Marked neuron death
was noticed in cultures treated with 3-HK at a concentration as low as 1 micromolar. 3-HK can be hydrolyzed
by an enzyme (kynureninase) to alanine and 3-hydroxyanthranilic acid and eventually completely oxidized
to carbon dioxide and water through a complicated biochemical pathway. In mosquitoes, tryptophan is
oxidized to 3-HK, but, unlike in mammals and in some other species, mosquitoes do not produce a
kynureninase, thus blocking the hydrolysis of 3-HK, an essential step in the complete degradation
of 3-HK to carbon dioxide and water. Consequently, mosquitoes must dispose of 3-HK in a different
manner than mammals. To prevent 3-HK from accumulating, a highly efficient enzyme (a transaminase)
transforms the chemically reactive 3-HK to the chemically stable xanthurenic acid. This pathway
evolved specifically in mosquitoes and serves as an essential mechanism for 3-HK detoxification.
The objective of our research is to understand the structure/function relationship of the specific
transaminase involved in mosquito 3-HK detoxification. Because the 3-HK transaminase is essential
for mosquito survival, understanding its structural basis of catalysis may provide insight for future
mosquito control strategy.

Program Summary: Our research group is studying the molecular and cellular mechanism controlling
human innate immunity and inflammation. Human innate immunity serves as a radar surveillance system
capable of sensing danger and abnormal signals from the environment as well as signals from within
the human body. Proper activation of innate immunity is essential for host defense against invading
pathogens, wound healing following injury, as well as eradication of dead or malignant cancer cells.
However, excessive or abnormal innate immunity and inflammation leads to serious inflammatory diseases
such as cardiovascular disease, diabetes, asthma, rheumatoid arthritis, as well as neurological
inflammatory diseases. It is no surprise that the National Institutes of Health have recently put
together a major roadmap entitled “Inflammation is the common cause for human disease”. Despite
the significance of innate immunity and inflammation, the molecular and cellular mechanism
underlying this process is not clearly understood. Many cell surface receptors and associated
intracellular signaling molecules are critically involved in the proper regulation of human innate
immunity network. Our group has unraveled the function of several key intracellular proteins
essential for mediating the human innate immunity process. By employing techniques in experimental
molecular biology, targeted disruption of select genes in transgenic mice models, and gathering
genetic information from human patients, we are defining potential molecular targets for future
intervention of chronic human inflammatory diseases.

Program Summary: My laboratory focus on intracellular zoonotic parasites including
Toxoplasma gondii, Encephalitozoon cuniculi, Cryptosporidium parvum, Trypanosoma
cruzi, and Leishmania infantum. We examine aspects of the epidemiology, pathogenesis, immune
response, transmission, and treatment of these zoonotic protozoan parasites. Toxoplasma gondii has
long been known as a cause of congenital disease in humans and about 91% of the female population in the US
of childbearing age are at risk of developing infection with this parasite. Maternally infected children often
suffer from mental retardation, blindness, and vision and hearing problems. One aspect of my research is
examining the efficacy of new anti-protozoals in vitro and in vivo. My group is also interested in the biology
of the tissue cyst stage. We were the first to demonstrate that all stages of the complex T. gondii life
cycle could produce tissue cysts in cell culture and that all isolates had the ability to form tissue cysts in cell
culture. These findings ruled out the influence of the host immune system on the induction of tissue cyst
formation. We are currently developing an in vitro system to examine the effects of various chemotherapeutic
agents on tissue cysts. Tissue cysts are dormant stages and not susceptible to drugs that kill other stages of the
parasite. Stage conversion from tissue cyst containing slowly growing bradyzoites to rapidly multiplying
destructive tachyzoites is responsible for encephalitis in AIDS patients and in toxoplasmosis seen in organ
transplantation patients. We are collaborating with others on developing a vaccine against toxoplasmosis
with the knowledge that a vaccine that prevents clinical disease but allows for the production of tissue cysts
is of limited value. Toxoplasma gondii infection has recently been associated with schizophrenia in
humans and behavioral changes in rodents. Our future work will be to examine the effect of chronic infection
with T. gondii on the levels of neurotransmitters in the brains of mice.

Another area of focus of my research group is Encephalitozoon cuniculi. It is a microsporidian parasite
usually associated with disease in rabbits but fatal disease also occurs in dogs and immunocompromised humans.
We have developed new diagnostic tests for E. cuniculi and demonstrated the activity of several
disinfectants against the spores of this parasite. There are 3 strains of E. cuniculi and dogs have strain
III. Interestingly, most E. cuniculi infections in humans in the US have been from strain III associated
with dogs. Several outbreaks of fatal encephalitozoonosis have occurred in endangered monkey species in
Zoos and they are also caused by E. cuniculi strain III. We are currently examining the prevalence of
this parasite in dogs in the US and other regions of the world.

Program Summary: Bacterial pathogens are able to cause disease in humans because they can
colonize different parts of the body and, for some pathogens, secrete powerful toxins that damage
cells and tissues. The bacterial pathogen Clostridium perfringens, which causes gas gangrene and
food poisoning, is efficient at both of these aspects of the disease process. It colonizes the
human colon very efficiently and we are studying the mechanism it uses to attach itself to host
cells. We believe these bacteria use a type of pili, hair-like structures that stick out of the
surface of the bacterium, to attach to host cell surfaces. They not only use the pili for attachment,
but they can also use them to move along the surface of human cells with a gliding motion.
Our research centers on the mechanism of pili assembly and function, with the hope that we can
use the results to develop strategies to limit the ability of the bacterium to colonize human
tissues. C. perfringens also secretes large quantities of powerful toxins that kill host cells.
The other main area of research in our lab is to understand how the bacterium regulates the
synthesis of these toxins since they are the major mediator of disease. If we can develop
strategies that prevent the bacterium from making or secreting toxins, this would be a very
useful approach to cure the diseases caused by C. perfringens, which often do not respond
to antibiotics alone.

Program Summary: Dr. Meng’s research focuses on the development of vaccines against emerging,
re-emerging, and zoonotic viral diseases of public health and/or economic importance. His
laboratory studies multiple virus systems including the hepatitis E virus (the causative agent
of human hepatitis E, which is an important human pathogen), Type 2 porcine circovirus (which
is an emerging and economically important swine pathogen), and porcine reproductive and respiratory
syndrome virus (another economically important swine pathogen). This research has recently led
to the development and licensure of the first United State Department of Agriculture fully-licensed
vaccine, “Suvaxyan® PCV2 One Dose”, against a deadly global swine disease. This vaccine
will save the global swine industry millions of dollars each year from loss caused by the disease.

Program Summary: The emergence of multi- and extensively-drug-resistant tuberculosis (MDR and XDR TB) as a major threat to the world population calls for rapid development of new TB drugs; the last effective drug, which was specifically developed for treating TB, was introduced in 1966. The goal of our research is to identify new cellular targets in Mycobacterium tuberculosis, the causative agent of TB, for the development of new therapeutics for TB. We have taken two approaches: one involves laboratory-based microbial genetics, molecular biology and biochemistry investigations, and the other is a site-based study. For the first approach we have focused on the physiological role of coenzyme F420 in the mycobacteria and the structure-function relationships in GTP-dependent phosphoenolpyruvate carboxykinase (GTP-PEPCK). Coenzyme F420 is a deazaflavin derivative. It is structurally similar to flavins but functionally acts as a hydride transfer-restricted coenzyme similar to the nicotinamides. F420 is present in all known methanogenic archaea, but it is rare in the bacterial domain, where it is primarily found in Actinobacteria such as mycobacteria. All mycobacteria examined thus far contain F420, and these bacteria express an F420-specific glucose-6-phosphate dehydrogenase (Fgd). The use of Fgd-generated reduced F420 (F420H2) in the mycobacteria is unknown. Our on-going investigation indicates that F420H2 helps to protect mycobacterial cells from oxidative and nitrosative damages similar to those induced by the macrophages. We are currently characterizing the components of this defense system. We have identified an F420-dependent enzyme that oxygenates mycolic acids, which are critical components of the mycobacterial cell envelope. The complex architecture of the cell envelope helps to protect M. tuberculosis from the bactericidal effects of human immune cells and most synthetic antibacterial agents. GTP-PEPCK is a key enzyme for gluconeogenesis in M. tuberculosis and therefore is essential for the survival of M. tuberculosis within the granuloma in a dormant or latent stage. The latent form of M. tuberculosis is not sensitive to most of the currently used TB drugs. As a result, the treatment of TB requires a rather lengthy drug therapy, which has been the reason for patient non-compliance and consequent development of drug-resistant strains of M. tuberculosis. Our research on GTP-PEPCK is focused on determining the differences between the structure-function relationships of the mycobacterial and human enzyme and thereby identifying the avenues for developing inhibitors for the M. tuberculosis GTP-PEPCK that will not affect the human enzyme. The site-based study utilizes clinical strains of M. tuberculosis isolated at the Rotinsulu Pulmonary Hospital (Bandung, Indonesia); this work represents collaboration between the Virginia Bioinformatics Institute (our group and the laboratory of Dr. Stephen Eubank), Institut Teknologi Bandung and Rotinsulu Pulmonary Hospital. The project goal is to determine the genetic and biochemical basis for the development of more virulent and MDR or XDR strains of M. tuberculosis. The project is based on the hypothesis that population lifestyles (economic status, mobility, environment) and treatment methodologies determine the immune system of a patient and chemical environment within the infected immune cells and promote changes in the genome of the pathogen which lead to increased virulence and drug resistance in TB.

The bacteria Staphylococus aureus is a leading cause of community acquired infections, surgical site infections,
bovine mastitis and human skin infections. The increased occurrence of multi-drug resistant strains necessitates the identification
of new mechanisms for controlling this pathogen. S. aureus causes disease in the human by producing toxins and by invading epithelial
cells (EC). EC are implicated in the production of coagulatory proteins to maintain hemostasis. Unfortunately, S. aureus can alter
host inflammatory and coagulatory responses by production of numerous virulence factors. We believe that intracellular invasion and
persistence within host cells enables S. aureus to manipulate the host immune response to its advantage, causing abscess formation and
chronic infections. One of our goals is to understand the basic immune and coagulatory responses of EC during infection with S. aureus.

We believe that within both bovine and human population, certain individuals are susceptible and others are resistant to S. aureus infection.
The bovine population, like humans, is naturally exposed to S. aureus. However, unlike a human model, our animal model provides a detailed
history of infection status and a catalogued collection of the S. aureus strains that caused these infections. Using the bovine population
we hope to identify antigens that stimulate immune memory and are candidates for vaccine development.

Program Summary: Mosquito-borne virus infections are a tremendous worldwide public health burden.
Mosquito-borne pathogens are maintained in nature through complex transmission cycles that
involve vertebrate hosts and mosquito vectors. While infection of the vertebrate host is acute
and often associated with disease, a hallmark of arthropod-borne virus (arbovirus) infections in
the mosquito is a general lack of pathology. Mosquito-borne viruses would not survive in nature if
they adversely affected the mosquito host, as they are dependent on this disease vector for
transmission. Therefore, a glaring deficiency in our understanding of arboviral disease transmission
has long been the paucity of information on how mosquito cells are able to resist the pathogenic
potential of arboviruses. Thus, the focus of my research program is on understanding the interactions
occurring between the virus and vector that result in the establishment and persistence of non-pathogenic
infections in the mosquito host. The information obtained from these studies will improve our ability to
predict and prevent arboviral disease epidemics. In addition, a strategy that would replace natural
populations of mosquitoes with genetically modified mosquitoes is currently being investigated for
controlling these important pathogens. Understanding the genetic components controlling the pathogenic
potential of arboviruses may be useful in such a strategy. For example, it may be possible to create
mosquitoes that would be rapidly killed when infected with an arbovirus. Thus, in the future,
a more complete understanding of how persistent arbovirus infections are established in the vector
host may provide a basis for human intervention of arboviral disease transmission.

Program Summary: Each year in the United States, 5.2 million illnesses
are attributed to food-borne bacteria. Two common bacterial food-borne pathogens, Salmonella
enterica and Escherichia coli O157:H7 are responsible for an estimated 1.4 million and 79 thousand
illnesses each year, respectively according to the Centers for Control and Prevention. Fourteen
percent of all food-borne illness outbreaks reported in North America could be linked directly to
minimally processed fruit and vegetables.

Even though produce may be contaminated during growth, harvest, processing, distribution or
final preparation, these outbreaks have raised concerns about the pre-harvest colonization by human
pathogens including S. enterica and E.coli O157:H7. However, little is known about the ecology and
mechanisms used by human pathogens to survive the stressful conditions in environment (soil, water,
surface of the plant). The ability of a human pathogen to colonize a plant is influenced not only by
environmental stresses such as temperature, exposure to UV radiation and dehydration, but also by
the interaction with the native species of plant microbiota. By identifying antagonistic or permissive
members of the produce microbiota we may develop control strategies that make use of such beneficial
bacteria to control growth and survival of enteric pathogens on produce allowing for design of effective
packaging and control procedures post-harvest.

Recent outbreaks associated with ready to eat, bagged spinach indicate that human pathogens
survive the modified atmosphere conditions designed to prolong shelf life. The relatively small
populations of S. enterica serotypes on plants and low infectious dose of Salmonella (as few as 100)
in produce linked outbreaks (1) suggests that physiological adaptation to plant associated factors
may increase survival on both a plant and human host. The expression of environmental survival
and virulence genes on the plant surface may adapt some bacteria to survive in harsh stomach and
intestinal fluids and attach to human cells, increasing the severity of illness. We will compare the
ability of produce outbreaks associated serovars of S. enterica and E.coli O157:H7 to adhere and
invade human Caco-2 cells when grown in association with plants and other food matrices. It is
unlikely that all human pathogens respond identically so it will be necessary to characterize survival
and genetic response of several strains of S. enterica and E.coli O157:H7 isolated from
the environment,
animal and clinical sources. These differences in survival, host specificity, or expression of virulence
genes likely lie within specific regions of the genome, necessitating a combination of molecular
subtyping methodologies and comparative molecular techniques. By identifying genes responsible for
survival and virulence we will enhance our ability to develop intervention strategies and interpret
subtyping data used to trace food-borne outbreaks.

Identifying the mechanisms by which microbes survive is vital both for disease control and the
extension of basic science. Additional research on the survival and response to environmental and
minimal processing conditions may reveal uncharacterized mechanisms of pathogenesis, will improve
our understanding of the spectrum of Salmonella diseases, and will enhance our ability to develop
intervention strategies.

Program Summary: Bacteria are major agents causing illness and death in
humans and other animals.
We study two aspects of bacterial growth and survival that have great effects on the ability of bacteria
to cause disease: the formation of their peptidoglycan cell wall and the formation of dormant spores.
Synthesis of the bacterial cell wall has traditionally been the best target for antibiotic development.
It is the target of penicillin, vancomycin, and other widely used drugs. Cell wall synthesis is still
considered an outstanding target since it is highly conserved across virtually all bacterial species.
Our studies on the precise roles of a variety of proteins in cell wall synthesis will contribute to the
rational design of new classes of antibiotics. Formation of spores allows certain bacteria to survive
in and invade habitats unavailable to other species and, thus, to affect human health. The spores of
Bacillus anthracis are the infectious agent for anthrax, and the sporulation by Clostridium perfringens
is required for this species to cause both food poisoning and gangrene. We study spore structure in
both of these species, specifically the unique spore peptidoglycan wall, in order to determine how this
structure contributes to the ability of spores to survive high heat and other treatments that normally
kill all other cell types and how this structure is degraded when the spores are ready to germinate and
cause disease. Our studies will contribute to the development of better methods for cleaning
spore-contaminated sites and preventing disease.

Program Summary: Influenza virus and other respiratory pathogens continue
to cause widespread
disease affecting not only humans but also numerous animal species. At particular risk are the elderly.
With the emergence of the “Bird Flu”, there is an increased risk of disease which could culminate in
broad economic disturbances throughout the U.S. and globally. Vaccination still represents the most
viable option for controlling viral diseases, including influenza. A major focus of our program is to
develop newer, more protective vaccines that provide long-lasting protection to humans and animals
against emerging viral pathogens, particularly influenza. One target group that we are focusing on
is the elderly. The rising elderly population in the U.S. will increase medical care costs that are
already overstretched. By developing vaccines targeting the elderly, we hope to significantly reduce
health care costs associated with respiratory viruses. Ideally, enhanced protective vaccines should
result in less hospital/physician visits, less absences from work, and reduced health care costs overall.
Finally, our program is seeking new ways to utilize naturally occurring viruses as a means to selectively
target cancer cells within the body and destroy them. This represents a new and exciting area of research
that offers enormous potential in treating advanced cancer.

Program Summary: We are interested in using chemistry to understand biological processes. Central
to our theme is organic chemistry as a tool that intersects with molecular life sciences, such as
molecular and cell biology. Our primary focus is the development of chemical toolboxes to address
problems in biology. Currently, our work is aimed at discovering and developing novel molecular entities
that can be used as probes or as therapeutics for disease states (Parkinson’s and Alzheimer’s disease)
that are not efficiently addressed using conventional small molecule drugs. We are also interested in
the search for new strategies in combating infectious diseases such as malaria and influenza.
In organic chemistry, we are employing a chemical biology approach in evolving nucleic acid polymers such
as RNA to discover molecular scaffolds that can catalyze chemical reactions that are environmentally
friendly. One of our goals is to use modular RNA to perform the total synthesis of natural products,
where one product can arise from a complex pool of starting materials.

Project Summary: The bacterium Pseudomonas aeruginosa is an opportunistic pathogen that causes a
number of life threatening infections in predisposed individuals. For instance, chronic lung infections
by P.aeruginosa are the major cause of mortality in cystic fibrosis patients. Generally, P.aeruginosa
infections can follow two distinct paths: acute and chronic infections. Acute infections are characterized
by a rapid and severe disease progression. The hallmark of this infection path is the type III secretion
system, a syringe-like channel, employed by P.aeruginosa to export a number of virulence factors that
suppress the host immune response. Chronic infections, on the other hand, follow a different, but no
less destructive path. The characteristic feature of chronic infections is the formation of protective
biofilms that shield the bacterial colonies. Biofilms constitute a formidable physical barrier that
not only protect P.aeruginosa from the host immune system but also impart dramatically increased antibiotic
resistance to the bacterium. We study the regulatory mechanisms that control both the type III
secretion system and biofilm formation. We use an integrated approach for our work that combines
structural biology, biochemical studies, and microbiology. Our long term goal is to aid the development
of new therapeutic options against P.aeruginosa through discovery of novel anti-microbial agents.

Program Summary: More than one million human lives are lost each year by malaria, a disease
transmitted exclusively by the Anopheles mosquito. Some of the most effective public-health measures
against vector-borne diseases throughout history have been those targeted at the vector. However,
because of growing insecticide resistance, the available strategies for alleviating the impact of
malaria are now insufficient. In fact, partially because of global warming, increased air transportation,
and the ability of mosquitoes to quickly adapt to new habitats, the public-health burden of malaria is
increasing and expanding. There is an urgent need to explore novel strategies for vector-based disease
control. Ecological adaptations of vectors can significantly increase malaria transmission.
For example, mosquitoes that are adapted to an arid climate can occupy larger geographic regions
and human dwellings. Ecological, behavioral, and physiological adaptations related to malaria
transmission are often associated with genome rearrangements. My research aims to understand the
role of genome rearrangements in mosquito evolution, adaptation, and ability to transmit malaria
parasites. The ultimate goal of this research is to develop a novel genomics-based approach for
vector control.

Project Summary: My laboratory is developing and testing vaccines against intracellular
pathogens. We are using a current USDA approved cattle vaccine, B. abortus RB51, developed at
the Center for Molecular Medicine and Infectious Diseases at Virginia Tech, as a vector to
express protective antigens against other infectious agents. We are developing and testing
RB51-Neospora caninum (RB51-NC) recombinant candidate vaccines in both a lethal and a pregnant
mouse model. Three candidate RB51-NC recombinant vaccines have shown promise in one, or both,
of these models. Flagellin, a filament protein that forms bacterial flagellum, appears to
function as an excellent adjuvant for the intranasal route of vaccine delivery and induces
high levels of antibodies against F1. It has been found to provide protection against an
aerosol challenge of Yersinia pestis, the causative agent of bubonic plague, at 150 times
the lethal dose. Similar studies are being conducted using the V antigen as the initiator
and we are in the process of analyzing the results. Some of the F1/V constructs, with flagellin
as the adjuvant, appear to provide protection. We are also studying the effect of aging on the
immune response against the intracellular pathogen B. abortus and we have seen some interesting
observations that are now being pursued. Recently, we have also initiated efforts to develop
targeted drug delivery against intracellular pathogens.

Program Summary: The Stevens lab works in the general field of molecular microbiology with
an emphasis on bacterial environmental sensing and gene regulation. The majority of the
research projects focus on the phenomenon of bacterial quorum sensing, a mechanism whereby
bacterial cells communicate with one another through the use of small molecules called autoinducers.
By understanding this mode of bacterial gene regulation, methods to manipulate it in ways
beneficial to society may be discovered. Our group currently studies the quorum sensing
systems of three different bacteria, one that establishes symbiotic/beneficial relationships
with animals, one that is an important plant/corn pathogen and one that is free-living in the
environment. In a separate project, we are exploring the development of antibiotic resistance
in environmental bacteria that are exposed to stress from common chemical contaminants.

Program Summary: According to the World Health Organization, cancer accounts for 7.1 million
deaths annually (12.5% of the global total). Approximately 20 million people suffer from cancer;
a figure projected to rise to 30 million in the next 20 years. The current options for treating
most cancers include radiation and chemotherapy, with their associated issues of efficacy and
quality of life. Cancer therapy using viruses is gaining importance and may be able to circumvent
some of these issues. Our program is directed towards genetically modifying a natural tumor
selective virus of chickens to treat human and animal cancer. Newcastle disease virus is a
major pathogen of chickens and other birds throughout the world. It causes only mild conjunctivitis
in humans. With reverse genetic technology we are attempting to create tumor-specific variants of
Newcastle disease virus so that it can have a high therapeutic index for various types of cancer.
For example, our recently funded project from the U.S. Department of Defense seeks to develop a
prostate-specific antigen targeted to Newcastle disease virus to treat prostate cancer. Similarly,
we are in the process of creating tailor-made viruses for various types of human and animal cancer.
We believe we will be able to address many of the difficulties in current cancer treatment
with this approach.

Program Summary: Mosquito transmitted diseases, such as malaria, dengue fever, and encephalitis,
claim millions of lives worldwide each year. My laboratory is using modern genomics and bioinformatics
tools to study the basic genetics and physiology of mosquitoes with the long-term goal of reducing
the burden of vector-borne infectious diseases. My research program covers three areas. The first
is mosquito transposable elements (TEs), which are mobile genetic elements that have the ability
to replicate and spread in the genome. Our objectives are to understand the fundamental biology of
TEs and their genomic and evolutionary impacts as well as to explore the applications of TEs as
molecular tools to manipulate mosquito genomes for the purpose of interrupting transmission of
pathogens. Second, we are conducting comparative genomics on a range of mosquitoes to provide
high-resolution identification of regulatory elements, uncover gene expansions/loss/rearrangements,
and reveal correlations between these genetic changes and biological adaptations which are being
tested experimentally. Finally, we have recently identified a number of mosquito-specific microRNAs
(miRNAs), which are a novel class of gene modulating molecules. miRNAs are ~22 nucleotide long
non-coding RNAs that modulate the expression of cellular genes by binding to cognate mRNAs for
cleavage or translational repression. miRNAs are widely distributed in metazoans and plants.
Many miRNAs exhibit finely controlled spatio-temporal expression profiles. Several of these
have been shown to be key regulatory molecules during embryonic development, stem cell division,
neurogenesis, heart development, haematopoietic cell differentiation, and cell death. miRNAs are
also implicated in cancer and control of viral infection. The level of several miRNAs changed
2-3 fold in mosquitoes after a blood meal, according to our preliminary miRNA array analyses
using whole body samples. We are testing the hypothesis that a small number of miRNAs are among
the key factors regulating tissue and temporal specific response to blood feeding during the
mosquito gonotrophic cycle and other miRNAs may be involved in mosquito-pathogen interactions.

Program Summary: The cell division cycle (CDC) is the sequence of events whereby a growing
cell makes new copies of all its parts and divides them, more-or-less, evenly between two daughter
cells so that each daughter contains all the information and machinery necessary to repeat the
process. The CDC is a fundamental process of life, underlying all biological growth,
development, and reproduction. Mistakes and problems in cell growth and division underlie
many human health problems, including cancer, tissue regeneration, and infectious diseases.
In the same way that an engineer must understand the mechanical and/or electrical components
of a machine and how they interact in order to fix it when it’s broken, a life scientist
must understand the molecular components of the cellular control system and how they interact
in order to develop new drugs and therapies for the infirmities that stem from faulty controls.
Molecular biologists have identified many of these components (genes and proteins) and
interactions (biochemical reactions) for the basic processes of life, including the CDC.
My world-leading research group builds mathematical models of these control systems in
order to better understand the complex molecular interactions within living cells and
how they are perturbed in diseased states.

Program Summary: Pathogens of humans, animals, and plants are dynamic entities that
continuously evolve to overcome their hosts’ immune system or to become resistant to new drugs.
Even new pathogen variants with new life styles can arise. For example, the detrimental bubonic
plaque pathogen, Yersinia pestis, which is transmitted by flea bites, is believed to have evolved
from a mild pathogen, which was unable to be transmitted by fleas, only approximately 10,000 years
ago. Plant pathogenic bacteria use the same basic evolutionary mechanisms as human pathogens. We
found evidence that with the introduction of agriculture, some plant pathogens changed their life
style from being mild pathogens of many different plants (which made them competitive in natural
mixed – plant communities) to being highly aggressive pathogens of only one plant species (which
made them competitive in agricultural fields of single crops). Studying the basic evolutionary
mechanisms that plant pathogens used to become more aggressive can help us to predict the risk
that certain pathogens will become more aggressive in the future and to develop agricultural
and medical practices that reduce the risk of the evolution of new highly aggressive pathogens.

Program Summary: Nuclear magnetic resonance (NMR) spectroscopy is positioned today to address
new frontiers of science from materials research to soil science, from anatomy to physiology, and
from structural biology to proteomics. NMR provides investigators the ability to gain structural
information on the atomic level in systems that do not contain long range order and to obtain
dynamic information on a timescale that is unavailable by other techniques. Our laboratory focuses
on the development and application of modern state-of-the-art solid-state NMR techniques to
investigate the diverse problems in biological science and modern materials. Our particular
interests are the structures of proteins/peptides that are hard to solubilize or crystallize—as
is often the case for membrane proteins, amyloid fibrils, and protein/peptide aggregates.
These are impossible to approach by NMR in solution-state or X-ray crystallography. Present
research activities include: 1) determining the structures and dynamics of membrane-bound
antimicrobial peptides; 2) determining the structure and dynamics of HIV-1 Tat peptides
binding to liposomes and Jurkat cells to understand the intracellular delivery mechanism
of proteins and small colloidal particles into the cytoplasm across cell membranes; and 3)
determining the conformational and interfacial structures of protein-protein, protein-ligand,
and protein-DNA complexes that are hard to be crystallized.

Program Summary: Awareness and proper responses to changes in the environment is critical for
the survival of any biological entity. Bacteria, whether pathogenic or otherwise, are no exception.
Human pathogens generally behave differently when they are within our body from when they are outside.
This is partially because they sense the changes in nutrients, temperature and other things within the
unfortunate host. How do organisms so small manage to sense and respond to environmental changes to
either thrive in particular niches or to result in tremendous human suffering and misery? That is the
main question we address using the gram-negative soil bacterium Myxococcus xanthus. That is, how does
this bacterium see, smell or feel the changes in their surroundings and how do the cues they perceive
lead to changes in their behavior and metabolism?

Program Summary: Rotaviruses are the leading cause of severe gastroenteritis in infants and
children worldwide. Probiotics, such as Lactobacilli, have been shown to reduce the severity of
rotavirus diarrhea; however the immunologic mechanisms have not been clearly defined. Colonization
of the human intestine with commensal microbes is hypothesized to drive the maturation of the
mucosal immune system during neonatal life, but the mechanisms are unknown. A goal of our
laboratory is to define the impact of colonization of the intestine by probiotic commensal
microbes on development of the mucosal immune system and innate and adaptive immune responses
to enteric virus infections and to clarify the immunological mechanisms involved using
gnotobiotic pigs colonized with two Lactobacillus strains used in the food industry.

Program Summary: Most female mosquitoes need to feed on vertebrate blood and use the nutrients
for their own egg production. During blood feeding, mosquitoes transmit many devastating diseases,
such as malaria, dengue fever, filariasis, and West Nile encephalitis. The causative pathogens have
developed exquisite strategies to exploit mosquitoes to complete their own life cycles and, at the
same time, to evade the mosquito immune system to ensure their own survival. We are exploring various
strategies to control these emerging or resurging mosquito-borne diseases. An effective approach
is to minimize the risk of infection by reducing mosquito populations. In the face of the growing
pesticide resistance detected in field populations of mosquito vectors, new environmentally safe
chemicals are needed to kill mosquitoes at various developmental stages. Understanding how mosquito
endogenous growth regulators exert their function will facilitate discovery of chemicals that repress
or block the normal growth and development of the mosquito. Another promising approach is to use
genetic engineering to eliminate or decrease the vector competence of mosquitoes. Some mosquitoes
are refractory to infections of pathogens in nature. Comparing gene expression of refractory and
susceptible mosquitoes in response to pathogen infections will shed light on the molecular nature
of mosquito-pathogen interactions and provide invaluable information on what protein factors in
mosquitoes are suitable for genetic intervention to adversely affect the pathogens.